Recombinant proteins are used to treat a number of human disorders including diabetes, neutropenia, anemia, and, more recently, chronic musculoskeletal disorders of the elderly. Muscle and bone wasting associated with aging can be attenuated using proteins such as growth hormone (GH), and insulin-like growth factor-1 (IGF-1), but their delivery by daily injection is not optimal since the proteins degrade rapidly in vivo and side effects occur. Cell-based delivery of proteins from genetically-modified implanted cells may provide a more effective and cost-saving alternative. The long-term objective of this project is to develop an effective, economic, and reversible cell-based delivery system for proteins based on a new form of ex vivo skeletal myofiber gene therapy. Cell Based Delivery, Inc. holds the exclusive licensing rights to technology whereby genetically modified myoblasts are tissue engineered into organized bioartificial skeletal muscles (BAMs) which can be implanted for the long-term systemic delivery of proteins. Phase I work demonstrated that murine BAMs secreting recombinant human GH (rhGH) reduced muscle atrophy in a murine hindlimb unloading model more effectively than daily rhGH injections. This was especially true for slow-twitch muscle which may be important for maintaining postural muscles in the frail elderly. In Phase II, we will extend the scientific program to isolate, grow, genetically engineer, and tissue engineer human muscle stem cells (myoblasts) from biopsied muscle of the frail elderly and patients with adult onset growth hormone deficiency. These groups represent large patient populations for which no standard therapy is in place. These studies will establish the scientific and technical feasibility of the BAM technology for the treatment of diseases of the elderly and will open wide commercial opportunities. PROPOSED COMMERCIAL APPLICATIONS: Cell Based Delivery, Inc. has developed a new form of muscle gene therapy for cell-based delivery of proteins to treat numerous chronic disorders such as muscle and bone wasting in the elderly. There is a very large market for the development of such delivery systems since the clinical need is large ($149 billion in socioeconomic costs in 1992), manufacturing high purity recombinant proteins for injection is expensive, and injections are not the optimal delivery method. Long-term cell-based delivery of these factors will result in considerable convenience to the patient and savings to the health care system.